TIR domain containing adaptor molecule 1 (TICAM1; formerly known as TIR-domain-containing adapter-inducing interferon-β or TRIF) is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of two TLR-associated signaling cascades, where the other one is dependent upon a MyD88 adapter.[5]
Toll-like receptors (TLRs) recognize specific components of microbial invaders and activate an immune response to these pathogens. After these receptors recognize highly conserved pathogenic patterns, a downstream signaling cascade is activated in order to stimulate the release of inflammatory cytokines and chemokines as well as to upregulate the expression of immune cells. All TLRs have a TIR domain that initiates the signaling cascade through TIR adapters. Adapters are platforms that organize downstream signaling cascades leading to a specific cellular response after exposure to a given pathogen.[6]
TICAM1 is primarily active in the spleen and is often regulated when MyD88 is deficient in the liver, indicating organ-specific regulation of signaling pathways. Curiously, there is a lack of redundancy within the TLR4 signaling pathway that leads to microbial evasion of immune response in the host after mutations occur within intermediates of the pathway.[7] Three TRAF-binding motifs present in the amino terminal region of TICAM1 are necessary for association with TRAF6. Destruction of these motifs reduced the activation of NF-κB, a transcription factor that is also activated by the carboxy-terminal domain of TICAM1 in the upregulation of cytokines and co-stimulatory immune molecules. This domain recruits receptor-interacting protein (RIP1) and RIP3 through the RIP homotypic interaction motif. Cells deficient for RIP1 gene display attenuated TLR3 activation of NF-κB, indicating the use of the RIP1 gene in downstream TICAM1 activation, in contrast to other TLRs that use IRAK protein for the activation of NF-κB.[8]
Areas of researchedit
Investigations into the function of TICAM1 are of great significance to various fields of biomedical research. The pathogenesis of infectious disease, septic shock, tumor growth, and rheumatoid arthritis all have close ties with TLR signaling pathways, specifically to that of TICAM1 . Better understanding of the TICAM1 pathway will be therapeutically useful in the development of vaccines and treatments that can control associated inflammation and antiviral responses. Experiments involving wild-type and TICAM1-deficient mice are critical for understanding the coordinated responses of TLR pathways. It is necessary to study the coordinated effects of these pathways in order to understand the complex responses initiated by TICAM1.[9]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000127666 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000047123 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Palsson-McDermott, Eva M.; O'Neill, Luke A. J. (2004). "Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4". Immunology. 113 (2): 153–162. doi:10.1111/j.1365-2567.2004.01976.x. PMC1782563. PMID 15379975.
^Guo B, Cheng G (2007). "Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK". J. Biol. Chem. 282 (16): 11817–26. doi:10.1074/jbc.M700017200. PMID 17327220.
^Palsson-McDermott, Eva and Luke A J O’Neill (2004) Immunology. 113(2) 153-162
ticam1, domain, containing, adaptor, molecule, formerly, known, domain, containing, adapter, inducing, interferon, trif, adapter, responding, activation, toll, like, receptors, tlrs, mediates, rather, delayed, cascade, associated, signaling, cascades, where, o. TIR domain containing adaptor molecule 1 TICAM1 formerly known as TIR domain containing adapter inducing interferon b or TRIF is an adapter in responding to activation of toll like receptors TLRs It mediates the rather delayed cascade of two TLR associated signaling cascades where the other one is dependent upon a MyD88 adapter 5 TICAM1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2M1X 2M63 3RC4 4BSX 4C0M 5JELIdentifiersAliasesTICAM1 IIAE6 MyD88 3 PRVTIRB TICAM 1 TRIF toll like receptor adaptor molecule 1 TIR domain containing adaptor molecule 1External IDsOMIM 607601 MGI 2147032 HomoloGene 8605 GeneCards TICAM1Gene location Human Chr Chromosome 19 human 1 Band19p13 3Start4 815 932 bp 1 End4 831 712 bp 1 Gene location Mouse Chr Chromosome 17 mouse 2 Band17 17 DStart56 576 319 bp 2 End56 583 786 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inparotid glandgastrocnemius muscleascending aortaskin of abdomenbody of stomachright lobe of livermonocyteright coronary arterypopliteal arteryduodenumTop expressed injejunumileumduodenumlacrimal glandepithelium of stomachurethrafemale urethrayolk saccolonmale urethraMore reference expression dataBioGPSn aGene ontologyMolecular functionsignal transducer activity protein binding protein kinase bindingCellular componentcytosol ripoptosome autophagosome endosome membrane cytoplasmic vesicleBiological processresponse to exogenous dsRNA immune system process positive regulation of nitric oxide biosynthetic process positive regulation of natural killer cell activation macrophage activation involved in immune response response to lipopolysaccharide positive regulation of B cell proliferation positive regulation of NF kappaB transcription factor activity defense response to virus positive regulation of interleukin 6 production positive regulation of tumor necrosis factor production positive regulation of I kappaB kinase NF kappaB signaling positive regulation of B cell activation positive regulation of protein binding inflammatory response I kappaB kinase NF kappaB signaling positive regulation of protein ubiquitination regulation of protein homodimerization activity positive regulation of type I interferon production MyD88 independent toll like receptor signaling pathway lipopolysaccharide mediated signaling pathway signal transduction necroptosis apoptotic signaling pathway apoptotic process negative regulation of MyD88 independent toll like receptor signaling pathway innate immune response positive regulation of autophagy TRIF dependent toll like receptor signaling pathway cellular response to lipopolysaccharideSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez148022106759EnsemblENSG00000127666ENSMUSG00000047123UniProtQ8IUC6Q80UF7RefSeq mRNA NM 182919NM 014261NM 001385678NM 001385679NM 001385680NM 174989RefSeq protein NP 891549NP 778154Location UCSC Chr 19 4 82 4 83 MbChr 17 56 58 56 58 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseToll like receptors TLRs recognize specific components of microbial invaders and activate an immune response to these pathogens After these receptors recognize highly conserved pathogenic patterns a downstream signaling cascade is activated in order to stimulate the release of inflammatory cytokines and chemokines as well as to upregulate the expression of immune cells All TLRs have a TIR domain that initiates the signaling cascade through TIR adapters Adapters are platforms that organize downstream signaling cascades leading to a specific cellular response after exposure to a given pathogen 6 Contents 1 Structure 2 Areas of research 3 References 4 External linksStructure editTICAM1 is primarily active in the spleen and is often regulated when MyD88 is deficient in the liver indicating organ specific regulation of signaling pathways Curiously there is a lack of redundancy within the TLR4 signaling pathway that leads to microbial evasion of immune response in the host after mutations occur within intermediates of the pathway 7 Three TRAF binding motifs present in the amino terminal region of TICAM1 are necessary for association with TRAF6 Destruction of these motifs reduced the activation of NF kB a transcription factor that is also activated by the carboxy terminal domain of TICAM1 in the upregulation of cytokines and co stimulatory immune molecules This domain recruits receptor interacting protein RIP1 and RIP3 through the RIP homotypic interaction motif Cells deficient for RIP1 gene display attenuated TLR3 activation of NF kB indicating the use of the RIP1 gene in downstream TICAM1 activation in contrast to other TLRs that use IRAK protein for the activation of NF kB 8 Areas of research editInvestigations into the function of TICAM1 are of great significance to various fields of biomedical research The pathogenesis of infectious disease septic shock tumor growth and rheumatoid arthritis all have close ties with TLR signaling pathways specifically to that of TICAM1 Better understanding of the TICAM1 pathway will be therapeutically useful in the development of vaccines and treatments that can control associated inflammation and antiviral responses Experiments involving wild type and TICAM1 deficient mice are critical for understanding the coordinated responses of TLR pathways It is necessary to study the coordinated effects of these pathways in order to understand the complex responses initiated by TICAM1 9 References edit a b c GRCh38 Ensembl release 89 ENSG00000127666 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000047123 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Palsson McDermott Eva M O Neill Luke A J 2004 Signal transduction by the lipopolysaccharide receptor Toll like receptor 4 Immunology 113 2 153 162 doi 10 1111 j 1365 2567 2004 01976 x PMC 1782563 PMID 15379975 nbsp Guo B Cheng G 2007 Modulation of the interferon antiviral response by the TBK1 IKKi adaptor protein TANK J Biol Chem 282 16 11817 26 doi 10 1074 jbc M700017200 PMID 17327220 Palsson McDermott Eva and Luke A J O Neill 2004 Immunology 113 2 153 162 Kawai Taro and Shizuo Akira 2004 Arthritis Res Ter 7 1 12 19 Ouyang X Negishi H Takeda R Fujita Y Taniguchi T Honda K 2007 Cooperation between MyD88 and TICAM1 pathways in TLR synergy via IRF5 activation Biochem Biophys Res Commun 354 4 1045 51 doi 10 1016 j bbrc 2007 01 090 PMID 17275788 External links editToll like receptor signaling pathway Reference pathway KO from the KEGG website TICAM1 protein human at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title TICAM1 amp oldid 1217278654, wikipedia, wiki, book, books, library,
